Application of albizzia chinensis triterpenic acid in preparation of products for preventing and / or treating alopecia

Abstract

The invention discloses an application of homogra albizzia triterpenic acid in preparation of a product for preventing and / or treating alopecia. The alopecia is preferably androgenetic alopecia. It is found for the first time that on one hand, the natural triterpenic acid can effectively inhibit the activity of 5 alpha-reductase, and generation of a pathogenic factor dihydrotestosterone is reduced from the source; on the other hand, human hair follicle dermal papilla cell apoptosis caused by dihydrotestosterone can be directly inhibited, and cell proliferation is promoted. The albizzia chinensis triterpenic acid can be applied to preparation of products for preventing and / or treating alopecia, new application of the albizzia chinensis triterpenic acid is provided, and a new choice is provided for preventing and treating alopecia.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of jacaranda triterpenoids in the preparation of products for the prevention and / or treatment of hair loss. Background Technology

[0002] Androgenetic alopecia (AGA) is the most common progressive hair loss disorder, affecting approximately half of all men and a significant proportion of all women worldwide. Its pathological mechanisms are primarily related to genetic background and androgen metabolism. A key step involves the irreversible conversion of testosterone to the more potent dihydrotestosterone (DHT) by 5α-reductase, highly expressed in hair follicles. DHT binds to the androgen receptor (AR) in the dermal papilla cells of the hair follicle, triggering a series of abnormal signal transduction pathways. This leads to follicle miniaturization, shortened anagen (growth) phase, and prolonged telogen (resting) phase, ultimately causing terminal hair to gradually transform into vellus hair, clinically manifesting as thinning and hair loss.

[0003] Currently, the primary first-line drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of AGA are finasteride and minoxidil. Finasteride is a 5α-reductase inhibitor that lowers DHT levels in serum and scalp through systemic administration. However, it may cause hormone-related side effects such as decreased libido and erectile dysfunction (occurring in approximately 2%-4%), and its efficacy is difficult to maintain after discontinuation, leading to decreased patient compliance. The mechanism of action of minoxidil is not fully understood, but it is generally believed to stimulate hair growth by opening potassium channels and promoting local blood circulation. However, its limitations include strong local irritation, which may cause contact dermatitis, dryness, and desquamation, as well as a "shedding phase," and a high relapse rate after discontinuation.

[0004] Given the aforementioned limitations of existing chemically synthesized drugs, the search for safe, effective, and multi-targeted alternative or adjuvant therapeutic components from natural products has become an important trend in AGA drug development. Plant-derived triterpenoids have attracted significant attention due to their broad-spectrum anti-inflammatory, antioxidant, and hormone-regulating activities.

[0005] Jacaranda mimosifolia ( Jacaranda copaia ) is a member of the Bignoniaceae family ( BignoniaceaeJacaranda is a fast-growing tree belonging to the genus Jacaranda, widely distributed in tropical regions such as the Amazon basin. Traditionally, its bark and leaves have been used to treat skin inflammation and infections. Modern phytochemical studies have shown that Jacaranda kaempferi is rich in triterpenoids, flavonoids, and iridoids. Among them, a series of pentacyclic triterpenoid acids (such as ursane and oleanane derivatives) isolated from its bark have been proven to have significant anti-inflammatory, antibacterial, and lipid peroxidation-inhibiting activities. However, to date, there have been no publicly reported or patented studies, either domestically or internationally, on the bioactivity and application of either crude extracts of Jacaranda kaempferi or isolated single triterpenoid acid components in the treatment or prevention of androgenetic alopecia.

[0006] Therefore, there is an urgent need in this field to develop a novel AGA treatment candidate that is derived from nature, has a clear mechanism of action, and has few side effects. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of the prior art and to disclose for the first time a new use of Jacaranda triterpenoid acid or its pharmaceutically acceptable salt in the prevention and / or treatment of hair loss and the promotion of hair growth.

[0008] To achieve the above objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides the use of jacaranda triterpenoid acid or a pharmaceutically acceptable salt thereof in the preparation of products for the prevention and / or treatment of hair loss.

[0009] Jacoumaric acid is a class of pentacyclic triterpenoid acidic compounds with a specific structure extracted and isolated from the plant Jacaranda copaia. Its English name is Jacoumaric acid, CAS number: 63303-42-4, and its molecular formula is C2. 39 H 54 O6, with a molecular weight of 618.84, has the following chemical structural formula:

[0010] Preferably, the hair loss is androgenetic alopecia.

[0011] Preferably, the product can promote hair growth.

[0012] Preferably, the mechanism of action of the product includes: inhibiting 5α-reductase activity, thereby reducing the production of dihydrotestosterone; and / or inhibiting apoptosis of human hair follicle dermal papilla cells induced by dihydrotestosterone and promoting the proliferation of these cells.

[0013] Preferably, the product is a medicine or a personal care product.

[0014] More preferably, the drug further includes pharmaceutically acceptable excipients. Its dosage form may be a topical dosage form (such as a solution, tincture, spray, cream, gel, or liniment) or an oral dosage form (such as a tablet, capsule, or oral liquid).

[0015] More preferably, the hair care products are selected from shampoos, conditioners, hair serums, hair oils, hair lotions, scalp creams, hair gels, hairsprays, hair masks, or eyebrow care products.

[0016] In a second aspect, the present invention provides a pharmaceutical composition for the prevention and / or treatment of hair loss, comprising a therapeutically effective amount of jacaranda triterpenic acid or a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable excipients.

[0017] The pharmaceutically acceptable pharmaceutical excipients mentioned above include any one or a combination of at least two of the following: sustained-release agents, excipients, fillers, binders, wetting agents, disintegrants, absorption promoters, surfactants, and lubricants. The combination of at least two is, for example, a combination of binders and excipients, a combination of binders and flavoring agents, a combination of binders and fillers, etc. Any other combination is also acceptable, and will not be elaborated here.

[0018] Thirdly, the present invention provides the use of Jacaranda triterpenoid acid or a pharmaceutically acceptable salt thereof in the preparation of an in vitro 5α-reductase activity inhibitor or a human hair follicle dermal papillary cell proliferation promoter.

[0019] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention provides a new use for jacaranda triterpenic acid. It is the first time that jacaranda triterpenic acid has been found to effectively improve hair loss and promote hair growth through a multi-target mechanism of action. It can be used to prepare drugs or hair care products for the prevention and / or treatment of hair loss, providing a new option for the prevention and treatment of hair loss.

[0020] This invention, through systematic in vitro enzyme inhibition experiments and cell model experiments, has demonstrated at multiple levels that the triterpenoid acid of Jacaranda mimosifolia can not only inhibit 5α-reductase at the source to reduce DHT production, but also directly antagonize DHT toxicity at the cellular level, protect and promote the vitality of key hair follicle cells, and achieve synergistic effects through multiple pathways, providing a solid scientific basis for its industrial development.

[0021] Jacaranda triterpenoids are derived from plants. Compared to synthetic drugs such as finasteride, they exhibit lower cytotoxicity and a lower risk of adverse reactions at effective concentrations, suggesting higher medication safety and patient compliance. Jacaranda triterpenoids can be isolated from various plants and traditional Chinese medicinal materials, ensuring the sustainable acquisition of their active ingredients and aligning with green and environmentally friendly development principles. Attached Figure Description

[0022] Figure 1 This is a graph evaluating the inhibitory effect of Jacaranda mimosifolia triterpenoid acid on 5α-reductase activity in Example 1 of the present invention; Figure 2 The figure shows the results of the effect of Jacaranda triterpenoid acid on the activity of normal human hair follicle dermal papillary cells (cytotoxicity experiment) in Example 2 of the present invention (compared with the control group, *P<0.05). Figure 3 The figure shows the results of the cell proliferation experiment on the effect of Jacaranda triterpenoid acid on the activity of human hair follicle dermal papilla cells induced by DHT in Example 2 of the present invention (compared with the blank group and the model group, ####P<0.0001; compared with the drug-treated group, **P<0.01; ***P<0.001; ****P<0.0001). Detailed Implementation

[0023] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments, but this does not limit the present invention in any way. Any modifications or improvements made based on the teachings of the present invention shall fall within the protection scope of the present invention.

[0024] The processes, conditions, reagents, and experimental methods used in implementing this invention, except as specifically mentioned below, are all common knowledge and general knowledge in the field, and this invention does not have any particular limitations. Experimental methods in the embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer.

[0025] Unless otherwise stated, all technical terms and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. However, in the event of any conflict, the specification containing the definitions shall prevail.

[0026] The following are some of the main sources of reagents and consumables in the examples: Jacaranda triterpenoids were purchased from Shanghai Yuanye Biotechnology Co., Ltd., with a purity of ≥95%. Human dermal papillary cells (HDPCs) were purchased from Cybio (Shanghai) Biotechnology Co., Ltd. Finasteride was purchased from Beijing Solarbio Technology Co., Ltd. Testosterone was purchased from Shanghai Jizhi Biochemical Technology Co., Ltd. 5α-reductase was extracted from the liver of SD rats; Reduced coenzyme II tetrasodium was purchased from Beijing Solarbio Science & Technology Co., Ltd.

[0027] Example 1: Evaluation of the effect of triterpenic acid in Jacaranda mimosifolia on inhibiting 5α-reductase activity (1) Three reaction systems were set up: blank control group (containing testosterone, 5α-reductase, reduced coenzyme II tetrasodium, and pure water), finasteride positive control group (containing finasteride, testosterone, 5α-reductase, reduced coenzyme II tetrasodium, and pure water), and drug group (containing jacaranda triterpenic acid, testosterone, 5α-reductase, reduced coenzyme II tetrasodium, and pure water).

[0028] (2) Each reaction system was continuously incubated at 37°C, and the OD value of the characteristic absorbance of reduced coenzyme II tetrasodium was continuously measured at 340 nm using a UV spectrophotometer. The rate of concentration decrease within 10 minutes was calculated based on its standard curve, and the enzyme activity was obtained by subtracting the rate of the blank group. The average value of the three parallel groups was taken.

[0029] Experimental results are as follows Figure 1 As shown, compared with the blank control group, the Jacaranda triterpenoid drug group showed significant 5α-reductase inhibitory activity, and its effect was comparable to that of the positive control drug finasteride, proving that it has a clear enzyme inhibitory effect.

[0030] Example 2: Effects of Jacaranda mimosifolia triterpenoids on the activity of normal human hair follicle dermal papillary cells (1) Preparation of 100 mg / mL Jacaranda triterpenic acid stock solution: Jacaranda triterpenic acid powder was weighed using an electronic balance and prepared into a stock solution with a concentration of 100 mg / mL using dimethyl sulfoxide (DMSO). The solution was then diluted with DMSO to different concentrations.

[0031] (2) Human dermal papillary cells (HDPCs) were digested with trypsin and then seeded into 96-well plates at a density of 1 × 10⁶ cells per well. 5 Cells were cultured overnight at 37°C. After cell adhesion, 0 μg / mL, 1.73125 μg / mL, 3.156325 μg / mL, 7.3125 μg / mL, 15.63 μg / mL, and 31.25 μg / mL of Jacaranda triterpenic acid were added to the corresponding culture dishes. After culturing at 37°C for 24 hours, cell viability was measured by CCK-8 assay, and then a fitted curve of cell survival rate corresponding to drug concentration was plotted using GraphPad Prism8.

[0032] The results are as follows Figure 2 As shown, within the tested concentration range, jacaranda triterpenoids exhibited minimal toxicity to human dermal papillary cells, with cell survival remaining at a high level, indicating good biocompatibility.

[0033] Example 3: Effect of Jacaranda mimosifolia triterpenoid acid on the activity of DHT-induced damaged human hair follicle dermal papillary cells Dihydrotestosterone (DHT) was dissolved in DMSO to prepare a stock solution of 100 mg / mL, which was then diluted with culture medium to obtain 31.25 μg / mL DHT. This stock solution was used to culture human dermal papillary cells (HDPCs) as the model group. The intervention group received 31.25 μg / mL DHT along with 1.73125 μg / mL, 3.156325 μg / mL, 7.3125 μg / mL, 15.63 μg / mL, and 31.25 μg / mL of Jacaranda triterpenic acid, respectively. The control group was treated with untreated standard culture medium. Cell viability was measured using the CCK-8 assay after 24 h of culture.

[0034] The results are as follows Figure 3 As shown, compared with the control group, the cell viability of the model group (DHT treatment) was significantly decreased. However, the cell viability of each intervention group was significantly improved compared with the model group, indicating that Jacaranda triterpenoids can effectively antagonize DHT-induced damage to human dermal papilla cells, inhibit apoptosis, and promote cell proliferation.

[0035] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. The use of jacaranda triterpenoid acid or a pharmaceutically acceptable salt thereof in the preparation of products for the prevention and / or treatment of hair loss.

2. The application according to claim 1, characterized in that, The hair loss described is androgenetic alopecia.

3. The application according to claim 1, characterized in that, The product can promote hair growth.

4. The application according to claim 1, characterized in that, The product inhibits dihydrotestosterone-induced apoptosis of human hair follicle dermal papilla cells and promotes the proliferation of these cells.

5. The application according to claim 1, characterized in that, The product inhibits 5α-reductase activity.

6. The application according to claim 1, characterized in that, The product in question is a medicine or a personal care product.

7. The application according to claim 6, characterized in that, The drug also includes pharmaceutically acceptable excipients.

8. The application according to claim 6, characterized in that, The hair care products are selected from shampoos, conditioners, hair serums, hair oils, hair lotions, scalp creams, hair gels, hairsprays, hair masks, or eyebrow care products.

9. A pharmaceutical combination for the prevention and / or treatment of hair loss, characterized in that, It contains kaempferia triterpenoid acid or its pharmaceutically acceptable salt and pharmaceutically acceptable excipients.

10. The use of Jacaranda triterpenoid acid or its pharmaceutically acceptable salt in the preparation of in vitro 5α-reductase activity inhibitors or human follicular dermal papillary cell proliferation promoters.

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